Prevalence of the c.35delG and p.W24X mutations in the GJB2 gene in patients with nonsyndromic hearing loss from North-West Romania

Lazăr, C.; Popp, R.; Trifa, A.; Mocanu, C.; Mihut, G.; Al-Khzouz, C.; Tomescu, E.; Figan, I.; Grigorescu-Sido, P.

doi:10.1016/j.ijporl.2009.12.015

« Previous Next »International Journal of Pediatric Otorhinolaryngology
Volume 74, Issue 4 , Pages 351-355, April 2010

Prevalence of the c.35delG and p.W24X mutations in the GJB2 gene in patients with nonsyndromic hearing loss from North-West Romania

C. Lazăr
- Department of Pediatrics I, University of Medicine and Pharmacy Cluj Napoca, 68 Motilor Street, Cluj-Napoca, Romania
- Corresponding author. Tel.: +40 264 592446/+40 722 785663; fax: +40 264 599463.
R. Popp
- Department of Medical Genetics, University of Medicine and Pharmacy Cluj-Napoca, 6 Pasteur Street, Cluj-Napoca, Romania
A. Trifa
- Department of Medical Genetics, University of Medicine and Pharmacy Cluj-Napoca, 6 Pasteur Street, Cluj-Napoca, Romania
C. Mocanu
- Department of Pediatric Otolaryngology, Clinical Pediatric Hospital Cluj-Napoca, 68 Motilor Street, Cluj-Napoca, Romania
G. Mihut
- Department of Pediatric Otolaryngology, Clinical Pediatric Hospital Cluj-Napoca, 68 Motilor Street, Cluj-Napoca, Romania
C. Al-Khzouz
- Department of Pediatrics I, University of Medicine and Pharmacy Cluj Napoca, 68 Motilor Street, Cluj-Napoca, Romania
E. Tomescu
- Department of Otolaryngology, University of Medicine and Pharmacy Cluj-Napoca, 3-5 Clinicilor Street, Cluj-Napoca, Romania
I. Figan
- Department of Pediatric Otolaryngology, Clinical Pediatric Hospital Cluj-Napoca, 68 Motilor Street, Cluj-Napoca, Romania
P. Grigorescu-Sido
- Department of Pediatrics I, University of Medicine and Pharmacy Cluj Napoca, 68 Motilor Street, Cluj-Napoca, Romania

Received 30 September 2009; received in revised form 20 December 2009; accepted 22 December 2009.

Abstract

Objective

In Central and South-Eastern European countries, the most frequent mutation types responsible for congenital nonsyndromic sensorineural hearing loss (NSHL) are c.35delG and p.W24X (15–55.8% and 2.5–4.3%, respectively). The aim of the study was to determine for the first time in Romania the prevalence of c.35delG and p.W24X mutations in patients with NSHL.

Material

75 unrelated children with NSHL from Transylvania (North-West Romania).

Methods

a. Audiological examination (otoscopy, tympanogram, acoustic otoemission and tonal audiogram or auditory evoked potentials); b. detection of the c.35delG (semi-nested-PCR, RFLP and ARMS-PCR analysis) and p.W24X (ARMS-PCR analysis) mutations.

Results

Audiological examination allowed the diagnosis of hearing loss of various degrees: moderate in 8 patients (10.7%), severe in 14 cases (18.7%), profound in 53 patients (70.6%). The number of reported mutation cases as against the number of alleles indicates a 33.3% frequency rate for c.35delG mutation and respectively 5.3% for p.W24X mutation. All 22 patients with 35delG/c.35delG genotype (19 patients), c.35delG/p.W24X genotype (2 patients) or p.W24X/p.W24X genotype (1 patient) presented profound/severe hearing loss.

Conclusion

Our study confirms that the frequency rate of the two mutations analyzed in patients with NSHL from North-West Romania is comparable to that seen in other Central and South-Eastern European countries. The homozygote or compound heterozygote states represent a major risk factor for profound or severe deafness. Audiological screening in newborns and genetic testing in confirmed congenital hypoacusis cases are compulsory for early therapeutic intervention (hearing prosthesis or cochlear implant) and genetic counselling.

Keywords: Connexin 26, c.35delG mutation, p.W24X mutation, Sensorineural hearing loss, Hereditary deafness